dbSNP rs11741808: HDAC3:c.1217+444T>C (chr5-141624764-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003883.4(HDAC3):c.1217+444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 154,658 control chromosomes in the GnomAD database, including 1,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1716 hom., cov: 31)

Exomes 𝑓: 0.18 ( 50 hom. )

Consequence

HDAC3
NM_003883.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

20 publications found

Variant links:

Genes affected

HDAC3 (HGNC:4854): (histone deacetylase 3) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]

HDAC3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

HDAC3 links:

ENSG00000228737 (HGNC:):

ENSG00000228737 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC3	NM_003883.4 link	c.1217+444T>C		intron_variant	Intron 14 of 14	ENST00000305264.8	NP_003874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC3	ENST00000305264.8 link	c.1217+444T>C		intron_variant	Intron 14 of 14	1	NM_003883.4	ENSP00000302967.3

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22567

AN:

152056

Hom.:

1716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.0837

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.182

AC:

452

AN:

2484

Hom.:

AF XY:

0.182

AC XY:

225

AN XY:

1238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.189

AC:

AN:

164

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.143

AC:

AN:

South Asian (SAS)

AF:

0.239

AC:

AN:

176

European-Finnish (FIN)

AF:

0.0946

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.186

AC:

346

AN:

1856

Other (OTH)

AF:

0.138

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.148

AC:

22580

AN:

152174

Hom.:

1716

Cov.:

AF XY:

0.147

AC XY:

10963

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.133

AC:

5530

AN:

41518

American (AMR)

AF:

0.162

AC:

2468

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

511

AN:

3472

East Asian (EAS)

AF:

0.0835

AC:

432

AN:

5176

South Asian (SAS)

AF:

0.192

AC:

923

AN:

4816

European-Finnish (FIN)

AF:

0.134

AC:

1423

AN:

10580

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10811

AN:

68010

Other (OTH)

AF:

0.159

AC:

337

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

997

1995

2992

3990

4987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

1258

Bravo

AF:

0.147

Asia WGS

AF:

0.144

AC:

502

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.84

(source)

DANN

Benign

0.52

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over